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Page 2 of 20 Jiang et al. Microbiome Res Rep 2024;3:47 https://dx.doi.org/10.20517/mrr.2024.12

the innovative clinical treatment of intestinal-related diseases.

Keywords: Akkermansia muciniphila, intestinal inflammation, colorectal cancer, metabolic disease, probiotic enzyme

INTRODUCTION
The intestinal microbiota is important in maintaining many significant physiological functions of the body,
e.g., assisting the host in digesting food and providing nutrients. The occurrence of a variety of diseases is
accompanied by the destruction of intestinal microbiota. In recent years, many intestinal diseases have been
found to be inextricably linked to intestinal microbiota disorders such as intestinal inflammation, functional
gastrointestinal diseases, and intestinal tumors. The development of liver diseases and metabolic syndromes
such as diabetes is also accompanied by ecological dysbiosis of the intestinal microbiota associated with the
development of intestinal diseases. In light of these factors, probiotics and their derivatives show promise in
addressing gut microbiota imbalances and potentially treating a wide array of diseases. Among the
[1]
identified next-generation beneficial bacteria , Akkermansia muciniphila (A. muciniphila, Akk) has been
recognized as a particularly promising candidate . Akk is an anaerobic intestinal bacterium belonging to
[2]
the Verrucomicrobiota, one of the commensal bacteria in the normal intestine. Akk was abundant in the
mucosal layer of the host intestine, especially in the cecum. It is prevalent in the gut of healthy adults and
[3]
infants, accounting for 1%-4% of the total intestinal microbiota colonized from early life . Akk is closely
related to the immune response, energy metabolism, microbial composition and intestinal mucin secretion.
It may also play an important role in most intestinal diseases such as intestinal inflammation, intestinal
tumors, functional gastrointestinal disorders, and other intestinal-related diseases such as diabetes, obesity
and liver disease . This article reviews the research history of Akk, its relationship with intestinal-related
[4-6]
diseases, and the possible mechanisms, with the aim to help lay the theoretical foundation for further
research on its specific treatment mechanisms and provide inspiration for the treatment and prevention of
related diseases.

THE RESEARCH HISTORY OF A. MUCINIPHILA
Akk is an anaerobic Gram-negative bacterium that is oval in shape, immobile and does not form
endospores. Akk belongs to the Verrucomicrobiota, Akkermansiaceae, and Akkermansia , and is the first
[7]
[8]
member and the only representative of Verrucomicrobiota in the human gut . The history of research on
Akk is not long [Figure 1], with its first isolation and identification in 2004 from human feces via anaerobic
culture by researchers from the Microbiology Laboratory of Wageningen University in the Netherlands . In
[7]
the first 5 years after its identification, there was only 1 report on Akk each year. Since 2010, Akk has been
gaining attention with significantly increasing studies on its genomic data and relationship with human
health and diseases. In 2007, a study using fluorescence in situ hybridization and real-time PCR analysis for
the 16S rRNA gene of Akk showed that it can be colonized in the intestine of infants, reach a level close to
the abundance in the intestine as healthy adults within 1 year, and gradually decrease in the elderly . In
[9]
2010, Png et al. found that Akk abundance was substantially reduced in the intestinal epithelium of Crohn’s
[10]
disease (CD) and ulcerative colitis (UC) patients . Furthermore, researchers sequenced the genome of Akk
ATCC BAA-835 in 2011 and found that its complete genome was composed of a 2,664,102 bp circular
[11]
chromosome with an average GC content of 55.8% . In the same year, studies found that Akk colonization
altered mucosal gene expression in germ-free mice, increased the expression of genes involved in immune
responses , and that the relative abundance of Akk was lower in children with autism . In 2012, Hansen
[12]
[13]
et al. found for the first time that the mucolytic bacterium Akk plays a protective role in the development of
autoimmune diabetes, especially in the infancy of mice . In 2013, Akk-derived extracellular vesicles were
[5]
found to be protective in the development of dextran sulfate sodium salt (DSS)-induced colitis . In 2014,
[14]